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Lysosomotropic amines modulate neutrophil calcium homeostasis
1Department of Medicine, Michigan State University, East Lansing 48824.
Journal of Cellular Physiology
|May 1, 1988
Summary
Lysosomotropic amines disrupt neutrophil calcium regulation by altering lysosomal pH, impacting calcium stores and neutrophil function. This highlights the critical role of acidic lysosomes in maintaining cellular calcium balance.
Area of Science:
- Cellular Biology
- Immunology
- Physiology
Background:
- Lysosomotropic amines alter lysosomal pH, affecting neutrophil function.
- pH and calcium regulation are interconnected in excitable cells.
Purpose of the Study:
- Investigate the impact of lysosomotropic weak bases on neutrophil calcium homeostasis.
- Determine the relationship between lysosomal pH and intracellular calcium release.
Main Methods:
- Treatment of neutrophils with lysosomotropic weak bases.
- Measurement of cytosol free calcium.
- Direct measurement of calcium release from permeabilized cells.
- Use of monensin to collapse transmembrane pH gradients.
Main Results:
- Weak bases caused significant calcium release from organelles, independent of inositol-triphosphate-sensitive stores.
- Monensin also induced organelle calcium release.
- Lysosomotropic amines modulated the initial calcium response to f-met-leu-phe, making it more transient.
- Resting cytosol calcium levels remained normal to minimally elevated.
Conclusions:
- An acidic intracellular compartment, like the lysosome, is crucial for neutrophil calcium homeostasis.
- pH-sensitive and inositol triphosphate-sensitive pools represent distinct intracellular calcium stores.
- Lysosomal pH perturbation contributes to the inhibition of neutrophil function by lysosomotropic amines.
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